title: Cell cycle-dependent subcellular translocation of the human DNA licensing inhibitor geminin.
abstract: Once per cell cycle replication is crucial for maintaining genome integrity. Geminin interacts with the licensing factor Cdt1 to prevent untimely replication and is controlled by APC/C-dependent cell cycle specific proteolysis during mitosis and in G1. We show here that human geminin, when expressed in human cells in culture under a constitutive promoter, is excluded from the nucleus during part of the G1 phase and at the transition from G0 to G1. The N-terminal 30 amino acids of geminin, which contain its destruction box, are essential for nuclear exclusion. In addition, 30 amino acids within the central domain of geminin are required for both nuclear exclusion and nuclear accumulation. Cdt1 overexpression targets geminin to the nucleus, while reducing Cdt1 levels by RNAi leads to the appearance of endogenous geminin in the cytoplasm. Our data propose a novel means of regulating the balance of Cdt1/geminin in human cells, at the level of the subcellular localization of geminin.
authors.affiliation: Laboratory of General Biology, School of Medicine, University of Patras, 26500 Rio, Patras, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Dimaki
authors.forename: Georgia
authors.initials: G
authors.lastname: Xouri
authors.forename: Ioanna-Eleni
authors.initials: IE
authors.lastname: Symeonidou
authors.forename: Chaido
authors.initials: C
authors.lastname: Sirinian
authors.forename: Hideo
authors.initials: H
authors.lastname: Nishitani
authors.forename: Stavros
authors.initials: S
authors.lastname: Taraviras
authors.forename: Zoi
authors.initials: Z
authors.lastname: Lygerou
mesh_terms: D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D004261:DNA Replication; D016193:G1 Phase; D064248:Geminin / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D061986:MCF-7 Cells; D008954:Models, Biological; D050505:Mutant Proteins / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D011485:Protein Binding; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism
chemical_list: C467199:CDT1 protein, human; D018797:Cell Cycle Proteins; C577995:GMNN protein, human; D064248:Geminin; D050505:Mutant Proteins; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins
keywords: Cdt1; Cell Compartmentation; Cell Cycle; DNA Replication; Geminin; Genome Stability; Genomic Instability; Licensing; Nuclear Exclusion; Nuclear Transport